EP0266303A2 - Antigestagènes pour inhibition de la synthèse utérine des prostaglandine - Google Patents

Antigestagènes pour inhibition de la synthèse utérine des prostaglandine Download PDF

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Publication number
EP0266303A2
EP0266303A2 EP87730107A EP87730107A EP0266303A2 EP 0266303 A2 EP0266303 A2 EP 0266303A2 EP 87730107 A EP87730107 A EP 87730107A EP 87730107 A EP87730107 A EP 87730107A EP 0266303 A2 EP0266303 A2 EP 0266303A2
Authority
EP
European Patent Office
Prior art keywords
antigestagens
hydroxy
dimethylamino
phenyl
uterine
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
EP87730107A
Other languages
German (de)
English (en)
Other versions
EP0266303A3 (en
EP0266303B1 (fr
Inventor
Walter Dr. Elger
Marianne Dipl.-Biologin Fähnrich
Sybille Dr. Dipl.-Biologin Beier
Krzysztof Dr. Chwalisz
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Bayer Pharma AG
Original Assignee
Schering AG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Schering AG filed Critical Schering AG
Priority to AT87730107T priority Critical patent/ATE78690T1/de
Publication of EP0266303A2 publication Critical patent/EP0266303A2/fr
Publication of EP0266303A3 publication Critical patent/EP0266303A3/de
Application granted granted Critical
Publication of EP0266303B1 publication Critical patent/EP0266303B1/fr
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
    • A61K31/567—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in position 17 alpha, e.g. mestranol, norethandrolone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the invention relates to the use of antigestagens for the production of medicaments for inhibiting uterine prostaglandin synthesis, in particular for the therapy and prophylaxis of dysmenorrheaic complaints.
  • Effective antigestagens are known, for example, from European patent 0057115 (Roussel-Uclaf).
  • RU 486 The 11 ⁇ - [4- (N, N-dimethylamino) phenyl] -17 ⁇ -hydroxy-17 ⁇ -propynyl-4,9 (10) -estradien-3-one, designated RU 486, was examined in particular detail. Information on the mechanism of action of RU 486 can be found in "Human Reproduction", Vol. 1 (1986), 107-110. Thereafter, the antigestagen blocks the progesterone activity and increases the formation of prostaglandin, the prostaglandin stimulating uterine contractility. Clinical examinations for the termination of pregnancy have already been carried out with RU 486.
  • Prostaglandins play a key role in normal and pathological menstruation: They are seen in relation to changes in the blood supply to the uterine lining and contractions of the uterus during labor during menstruation. Increased PG release and increased uterine contractions, which can be felt to be extremely painful, make up the essence of dysmenorrhea.
  • An inhibition of the uterine PG by antigestagens eliminates or at least significantly reduces the symptoms associated with dysmenorrhea. Since uterine PG synthesis takes place very substantially in the endometrium, it can also be expected that disorders and complaints resulting from endometriosis will also be favorably influenced by antigestagens.
  • the luteolysis of uterine PG at the end of the approximately 16-day cycle was blocked by antigestagens.
  • the result was a progression of the serum progesterone values that otherwise only exists in pregnancy.
  • the corresponding effects of the inhibited uterine PG production are not to be expected in humans after antigestagens, since in women the lifespan of the corpus luteum is not controlled by the uterus.
  • an inhibition of the uterine PG release can dampen the uterine motor function in the presence of dysmenorrhea.
  • the advantage of this therapeutic option is that a desirable level of inhibition is achieved without affecting the PG function in other organs.
  • a high degree of organ selectivity is achieved through the therapy of dysmenorrhea with antigestagens.
  • Antigestagens can be used when dysmenorrhoeic complaints begin, such as "pulling in the lower abdomen". It is sometimes useful to start therapy earlier in the luteal phase to achieve a sufficient level of inhibition.
  • the anti-gestagen treatment is generally carried out over 1 to 6, preferably 1 to 4 days, starting at the time of the menstruation.
  • the antigestagens are used in amounts of generally 2 to 50 mg, preferably 5 to 20 mg, 11 ⁇ - [(4-N, N-dimethylamino) phenyl] -17 ⁇ -hydroxy-17 ⁇ - (3-hydroxypropyl) -13 ⁇ -methyl-4.9 (10) -gonadien-3-one per day or a biologically equivalent amount of another antigagen.
  • the antigestagens can be applied locally, topically, enterally or parenterally, for example.
  • tablets, pills, capsules, pills, suspensions or solutions are particularly suitable, which can be prepared in the usual way with the additives and carrier substances customary in galenics.
  • vaginal suppositories or transdermal systems such as skin plasters are suitable.
  • One dosage unit contains about 2 to 50 mg 11 ⁇ - [(4-N, N-dimethylamino) phenyl] -17 ⁇ -hydroxy-17 ⁇ - (3-hydroxypropyl) -13 ⁇ -methyl-4.9 (10) -gonadien-3 -on or a biologically equivalent amount of another antigenic agent.
  • Non-gravid guinea pigs received 10 mg of 11 ⁇ - [(4-N, N-dimethylamino) phenyl] -17 ⁇ -hydroxy-17 ⁇ - (3-hydroxypropyl) -13 ⁇ - daily from the 8th to the 16th day of the approximately 16-day cycle. methyl-4,9 (10) -gonadien-3-one.
  • test substance was dissolved in 1 ml of benzyl benzoate / castor oil (1: 2) and injected subcutaneously.
  • the progesterone content in the serum was determined daily.
  • the increase in progesterone in the blood of animals treated with the anti-gestagen reflects an inhibition of the uterine PG release.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Urology & Nephrology (AREA)
  • Endocrinology (AREA)
  • Reproductive Health (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Steroid Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
EP87730107A 1986-09-26 1987-09-15 Antigestagènes pour inhibition de la synthèse utérine des prostaglandine Expired - Lifetime EP0266303B1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AT87730107T ATE78690T1 (de) 1986-09-26 1987-09-15 Antigestagene zur hemmung der uterinen prostaglandinsynthese.

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE3633244 1986-09-26
DE19863633244 DE3633244A1 (de) 1986-09-26 1986-09-26 Antigestagene zur hemmung der uterinen prostaglandinsynthese

Publications (3)

Publication Number Publication Date
EP0266303A2 true EP0266303A2 (fr) 1988-05-04
EP0266303A3 EP0266303A3 (en) 1989-12-20
EP0266303B1 EP0266303B1 (fr) 1992-07-29

Family

ID=6310705

Family Applications (1)

Application Number Title Priority Date Filing Date
EP87730107A Expired - Lifetime EP0266303B1 (fr) 1986-09-26 1987-09-15 Antigestagènes pour inhibition de la synthèse utérine des prostaglandine

Country Status (12)

Country Link
US (1) US5744464A (fr)
EP (1) EP0266303B1 (fr)
JP (1) JP2582088B2 (fr)
AT (1) ATE78690T1 (fr)
AU (1) AU605177B2 (fr)
DE (2) DE3633244A1 (fr)
DK (1) DK169162B1 (fr)
ES (1) ES2051766T3 (fr)
GR (1) GR3005467T3 (fr)
IE (1) IE66196B1 (fr)
IL (1) IL83967A (fr)
ZA (1) ZA877247B (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0310541A1 (fr) * 1987-10-01 1989-04-05 Schering Aktiengesellschaft Composés antigestagéniques et anti-oestrogéniques pour le déclenchement de la naissance et pour l'interruption de la grossesse ainsi que pour le traitement des troubles gynécologiques
EP0417003A2 (fr) * 1989-09-07 1991-03-13 Roussel-Uclaf Utilisation de composés antiprogestomimétiques pour favoriser l'ovulation
AT400298B (de) * 1989-11-15 1995-11-27 Roussel Uclaf Verwendung injizierbarer, biologisch abbaubarer mikrokugeln, verfahren zu ihrer herstellung und injizierbare suspensionen, die diese enthalten
LT5034B (lt) 1999-08-31 2003-07-25 Jenapharm Gmbh & Co. Kg Mezoprogestinai (progesteroninių receptorių moduliatoriai), skirti hormonų sąlygotų gėrybinių ginekologinių sutrikimų gydymui ir prevencijai

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19652408C2 (de) * 1996-12-06 2002-04-18 Schering Ag Steroidester, Verfahren zu ihrer Herstellung und ihre Verwendung zur Herstellung von Arzneimitteln
US20100249125A1 (en) * 2009-03-31 2010-09-30 The Texas A&M University System Inhibition of prostglandin e2 receptors for the treatment of endometriosis

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3077437A (en) * 1957-07-29 1963-02-12 George P Heckel Pregnanediol for treatment of premenstrual syndrome
US3666858A (en) * 1967-06-29 1972-05-30 Gordon Alan Hughes Utilization of gon-4-ene therapy in treatment of females and in growth stimulation
US4780461A (en) * 1983-06-15 1988-10-25 Schering Aktiengesellschaft 13α-alkyl-gonanes, their production, and pharmaceutical preparations containing same
DE3337450A1 (de) * 1983-10-12 1985-04-25 Schering AG, 1000 Berlin und 4709 Bergkamen Prostaglandine und antigestagene fuer den schwangerschaftsabbruch
DE3347126A1 (de) * 1983-12-22 1985-07-11 Schering AG, 1000 Berlin und 4709 Bergkamen 11ss-aryl-estradiene, deren herstellung und diese enthaltende pharmazeutische praeparate
DE3625315A1 (de) * 1986-07-25 1988-01-28 Schering Ag 11ss-(4-isopropenylphenyl)-estra-4,9-diene, deren herstellung und diese enthaltende pharmazeutische praeparate
DE3702383A1 (de) * 1987-01-23 1988-08-04 Schering Ag 11ss-alkinylestrene und -estradiene, deren herstellung und diese enthaltende pharmazeutische praeparate

Non-Patent Citations (9)

* Cited by examiner, † Cited by third party
Title
Acta Endocrinol (Suppl.), Band 114, Juni 1987, Seite 126, M. FAEHNRICH: "The influence of progesterone antagonists on PG-liberation in different uterine compartments", Insgesamt. *
ACTA ENDROCRINOL (Suppl.), Band 114, Juni 1987, Seite 126 M. FÄNRICH: "The influence of progesterone antagonists on PG-liberation in different uterine compartments" *
Acta Endrocrinol (Suppl.), Band 114, Juni 1987, Seiten 7,8, J. NEULEN et al.: "Influence of the antigestagens ZK 98.299 and ZK 98.734 on the production of prostaglandin F2alpha (PG F2alpha) and prostaglandin E2(PG E2) in human endometrium in vitro", Insgesamt. *
Am. J. Obstet. Gynaecol., Band 157 (4Pt2), Oktober 1987, Seiten 1065-1074, W. EIGER et al.: "Endometrial and myometrial effects of progesterone antagonists in pregnant guinea pigs", Seite 1071, rechte Spalte, letzter Abschnitt - Seite 1072, rechte Spalte, Zeile 12; Seite 1073, linke Spalte, letzter Abschnitt - Seite 1074, linke Spalte, Zeile 6. *
Br. J. Obstet. Gynaecol., Band 83, Nr. 3, Mai 1976, Seiten 337-341, E.A. WILLMAN et al.: "Studies in the involvement of prostaglandins in uterine symptomatology and pathology", Tabelle 2; Seite 340, linke Spalte, Zeilen 15-31. *
Comparative pharmacological studies on new progesterone-antagonists etc., Elger et al., Nichidoku-Iho, vol. 33, no. 4, 1990 *
J. Endocr., Band 77, 1978, Seiten 361-371, GB; J.B. MAATHUIS et al.: "Concentrations of prostaglandins F2 alpha and E2 in the endometrium throughout the human menstrual cycle, after the administration of clomiphene or an oestrogen-progestogen pill and in early pregnancy", Zusammenfassung; Seite 368, Zeilen 23-30. *
J. Obstet Gynaecol. Br. Commonw., Band 72, 1965, Seiten 185-192, V.R. PICKLES et al.: "Prostaglandins in endometrium and menstrual fluid from normal and dysmenorthoeic subjects", Seite 187, Abschnitt "II"; Seite 188, linke Spalte; Seiten 189-191: Abschnitt "Dysmenorrhoea"; Seite 191, Zusammenfassung. *
V.R. PICKLES et al.: "Prostaglandins in endometrium and menstrual fluid from normal and dysmenorrhoeic subjects" *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0310541A1 (fr) * 1987-10-01 1989-04-05 Schering Aktiengesellschaft Composés antigestagéniques et anti-oestrogéniques pour le déclenchement de la naissance et pour l'interruption de la grossesse ainsi que pour le traitement des troubles gynécologiques
EP0417003A2 (fr) * 1989-09-07 1991-03-13 Roussel-Uclaf Utilisation de composés antiprogestomimétiques pour favoriser l'ovulation
EP0417003A3 (en) * 1989-09-07 1991-12-04 Roussel-Uclaf Use of antiprogestomimetics for stimulating ovulation
AT400298B (de) * 1989-11-15 1995-11-27 Roussel Uclaf Verwendung injizierbarer, biologisch abbaubarer mikrokugeln, verfahren zu ihrer herstellung und injizierbare suspensionen, die diese enthalten
LT5034B (lt) 1999-08-31 2003-07-25 Jenapharm Gmbh & Co. Kg Mezoprogestinai (progesteroninių receptorių moduliatoriai), skirti hormonų sąlygotų gėrybinių ginekologinių sutrikimų gydymui ir prevencijai

Also Published As

Publication number Publication date
DK487287A (da) 1988-03-27
ATE78690T1 (de) 1992-08-15
GR3005467T3 (fr) 1993-05-24
AU7895087A (en) 1988-03-31
IE872578L (en) 1988-03-26
US5744464A (en) 1998-04-28
DE3780757D1 (de) 1992-09-03
DK169162B1 (da) 1994-09-05
IL83967A (en) 1992-11-15
JP2582088B2 (ja) 1997-02-19
AU605177B2 (en) 1991-01-10
EP0266303A3 (en) 1989-12-20
DE3633244A1 (de) 1988-03-31
EP0266303B1 (fr) 1992-07-29
ZA877247B (en) 1988-03-28
JPS63101326A (ja) 1988-05-06
DK487287D0 (da) 1987-09-16
IE66196B1 (en) 1995-12-13
ES2051766T3 (es) 1994-07-01
IL83967A0 (en) 1988-02-29

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